ZYNLONTA in combination with glofitamab
demonstrated clinically meaningful benefit with 94% best ORR and
72% CR rate
Safety data show no dose-limiting toxicities
(DLTs), no high-grade cytokine release syndrome (CRS) or high-grade
immune effector cell-associated neurotoxicity syndrome (ICANS)
across all patients
Company to host conference call today at
8:30 a.m. EST
LAUSANNE, Switzerland, Dec. 11,
2024 /PRNewswire/ -- ADC Therapeutics SA (NYSE:
ADCT), a commercial-stage global leader and pioneer in the field of
antibody drug conjugates (ADCs), today announced positive initial
data from the LOTIS-7 Phase
1b open-label clinical trial
evaluating the safety and efficacy of ZYNLONTA® in
combination with the bispecific antibody glofitamab
(COLUMVI™) in patients with relapsed or refractory
diffuse large B-cell lymphoma (r/r DLBCL).
"We are excited by the strong initial results observed with
ZYNLONTA plus glofitamab in second line plus patients with relapsed
or refractory DLBCL," said Mohamed
Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics.
"We believe these data support our hypothesis that combining these
two potent, approved, single-agent-drugs with complementary
mechanisms of action will yield additive or synergistic efficacy,
and a manageable safety profile given no overlapping
non-hematologic toxicities, enabling administration across care
settings. We are encouraged by the initial promising safety and
efficacy data at both doses tested in the expansion arm."
Initial Clinical Data from Phase 1b
LOTIS-7 Trial
LOTIS-7 is an ongoing Phase
1b global multicenter, multi-arm
study in patients with relapsed or refractory (r/r) B-cell
non-Hodgkin lymphoma (B-NHL) including Part 1 (dose escalation) and
Part 2 (dose expansion). As of the November
20, 2024 cutoff date, a total of 29
B-NHL patients from Part 1 and Part 2 across all dose levels
were treated and evaluated for safety.
An initial efficacy analysis was conducted on all 18 evaluable
2L+ DLBCL patients who received dose levels of 120 µg/kg (n=9) or
150 µg/kg (n=9) of ZYNLONTA plus the bispecific antibody
glofitamab:
- Best overall response rate (ORR) was 94% (17/18) as assessed by
Lugano criteria
- Complete response (CR) was achieved in 72% (13/18) and partial
response (PR) was achieved in 22% (4/18) of patients. Of those
achieving CR, 12 out of 13 remain in CR as of the cutoff date.
- Among patients treated with ZYNLONTA at the 150µg/kg dose (the
initial dose approved for ZYNLONTA as a monotherapy in 3L+
DLBCL patients), best ORR was 100% (9/9) and CR was achieved in 78%
(7/9) of patients
Encouraging efficacy data was observed across patients with
different numbers of lines and types of prior treatments and across
different histologies.
Initial safety data on all 29 patients suggest that ZYNLONTA
plus glofitamab is generally well tolerated with no DLTs across all
dose levels:
- Treatment emergent adverse events (TEAEs) of Grade 3 or higher
occurring in ≥ 5% of patients included neutropenia (24%),
lymphopenia (7%) and hypokalemia (7%)
- Cytokine Release Syndrome (CRS) of Grade 1 or 2 according
to ASTCT grading was observed in 34.5% of patients and resolved
with standard treatment. Low-grade Immune Effector Cell-Associated
Neurotoxicity Syndrome (ICANS) (Grade 2 according to ASTCT grading)
was observed in two patients and both had complete resolution of
symptoms. No Grade 3 or higher CRS or ICANS were observed.
- There were no Grade 5 TEAEs observed
"These compelling initial results support the potential of
ZYNLONTA plus the bispecific glofitamab to be a best-in-class
combination in a highly competitive market," said Ameet Mallik, Chief Executive Officer of ADC
Therapeutics. "We look forward to completing enrollment of dose
expansion in the first half of 2025 and plan to engage with
regulatory authorities on the path forward as data including
additional patients with longer follow-up become available."
Conference Call Information
To access the conference call, please register here. The
participant toll-free dial-in number is 1-800-836-8184 for
North America and Canada. It is recommended that you join 10
minutes before the event, though you may pre-register at any time.
A live webcast of the call will be available under "Events and
Presentations" in the Investors section of the ADC Therapeutics
website at ir.adctherapeutics.com. The archived webcast will be
available for 30 days following the call.
About LOTIS-7
LOTIS-7 is a Phase 1b global multicenter, multi-arm study in
patients with relapsed or refractory B-cell non-Hodgkin lymphoma
(B-NHL) including Part 1 (dose escalation) and Part 2 (dose
expansion). The three dosing arms include ZYNLONTA plus polatuzumab
vedotin, ZYNLONTA plus glofitamab, and ZYNLONTA plus mosunetuzumab
T-cell-engaging bispecific monoclonal antibodies (BsAbs).
Enrollment in LOTIS-7 includes Part 1
of the study with a 3+3 dose escalation in 3L/3L+ heavily
pre-treated patients with ZYNLONTA doses starting at 90 µg/kg and
then proceeding to 120 µg/kg and 150 µg/kg. Part 2 includes dose
expansion in 2L/2L+ large B-cell lymphoma in the ZYNLONTA plus
glofitamab arm at dose levels determined from Part 1 (120 µg/kg and
150 µg/kg of ZYNLONTA plus the approved dosing of glofitamab).
Primary endpoints of the study include safety and tolerability.
Secondary efficacy endpoints include ORR, DOR, CRR, PFS, RFS, and
OS as well as pharmacokinetics and immunogenicity.
For more information about the LOTIS-7 trial, visit clinicaltrials.gov
(NCT04970901).
About ADC Therapeutics
ADC Therapeutics (NYSE: ADCT) is a commercial-stage global
leader and pioneer in the field of antibody drug conjugates (ADCs).
The Company is advancing its proprietary ADC technology to
transform the treatment paradigm for patients with hematologic
malignancies and solid tumors.
ADC Therapeutics' CD19-directed ADC ZYNLONTA (loncastuximab
tesirine-lpyl) received accelerated approval by the FDA and
conditional approval from the European Commission for the treatment
of relapsed or refractory diffuse large B-cell lymphoma after two
or more lines of systemic therapy. ZYNLONTA is also in development
in combination with other agents and in earlier lines of therapy.
In addition to ZYNLONTA, ADC Therapeutics has multiple ADCs in
ongoing clinical and preclinical development.
ADC Therapeutics is based in Lausanne (Biopôle), Switzerland, and has operations in
London and New Jersey. For more information, please
visit https://adctherapeutics.com/ and follow the Company
on LinkedIn.
ZYNLONTA® is a registered trademark of ADC
Therapeutics SA.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995. In some cases you can identify
forward-looking statements by terminology such as "may", "will",
"should", "would", "expect", "intend", "plan", "anticipate",
"believe", "estimate", "predict", "potential", "seem", "seek",
"future", "continue", or "appear" or the negative of these terms or
similar expressions, although not all forward-looking statements
contain these identifying words. Forward-looking statements are
subject to certain risks and uncertainties that can cause actual
results to differ materially from those described. Factors that may
cause such differences include, but are not limited to: plans and
timelines for the clinical development for LOTIS-7, including the therapeutic potential,
clinical benefits and safety thereof; uncertainty whether future
data will be consistent with the initial data; expectations
regarding timing, success and future data announcements for
LOTIS-7; the expected cash runway
into mid-2026 the Company's ability to grow
ZYNLONTA® revenue in the
United States; the ability of our partners to commercialize
ZYNLONTA® in foreign markets, the timing and amount
of future revenue and payments to us from such partnerships and
their ability to obtain regulatory approval for
ZYNLONTA® in foreign jurisdictions; the timing and
results of the Company's or its partners' research and development
projects or clinical trials including LOTIS
5 and 7 and ADCT 602 as well as early research in certain
solid tumors with different targets, linkers and payloads; the
timing and results of investigator-initiated trials including those
studying FL and MZL and the potential regulatory and/or compendia
strategy and the future opportunity; the timing and outcome of
regulatory submissions for the Company's products or product
candidates; actions by the FDA or foreign regulatory authorities;
projected revenue and expenses; the Company's indebtedness,
including Healthcare Royalty Management and Blue Owl and Oaktree
facilities, and the restrictions imposed on the Company's
activities by such indebtedness, the ability to comply with the
terms of the various agreements and repay such indebtedness and the
significant cash required to service such indebtedness; and the
Company's ability to obtain financial and other resources for its
research, development, clinical, and commercial activities.
Additional information concerning these and other factors that may
cause actual results to differ materially from those anticipated in
the forward-looking statements is contained in the "Risk Factors"
section of the Company's Annual Report on Form 10-K and in the
Company's other periodic and current reports and filings with the
U.S. Securities and Exchange Commission. These statements involve
known and unknown risks, uncertainties and other factors that may
cause actual results, performance, achievements or prospects to be
materially different from any future results, performance,
achievements or prospects expressed in or implied by such
forward-looking statements. The Company cautions investors not to
place undue reliance on the forward-looking statements contained in
this document.
CONTACTS:
Investors
Marcy Graham
ADC Therapeutics
Marcy.Graham@adctherapeutics.com
+1 650-667-6450
Media
Nicole Riley
ADC Therapeutics
Nicole.Riley@adctherapeutics.com
+1 862-926-9040
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